It has been observed that pH of the reaction medium has an important influence on the kinetic properties of tyrosine hydroxylase. This enzyme appears to exert in at least two activity states. The highly active form (phosphorylated) has a low Km for the hydroxylase cofactor and pH optimum of 6.2, whereas the inactive form has a pH optimum of 5.8 and a poor affinity for the cofactor. We have observed that dopamine receptor blockade in vivo results in a rapid activation of tyrosine hydroxylase in the dopaminergic terminals in the striatum. Because of the differential pH optima, the maximum regulatory effect are seen at pH values higher than 6.2. This study has revealed important mechanisms underlying the mechanism of a number of antipsychotic drugs.